This research proposes to assess the biochemical role of glycerol kinase in the developing organism through investigations of the nature and impact of the inherited deficiency of this enzyme in man. These investigations will include the comparison of complementation between glycerol kinase deficient fibroblasts using polyethylene glycol-induced somatic cell hybridization, purification of human glycerol kinase to homogeneity followed by enzymologic characterization and preparation of antibody, investigation of organ and/or developmental specificity of glycerol kinase, evaluation of the functional importance of mitochondrial binding of this enzyme, and measurement of the metabolic consequences of glycerol kinase deficiency to other enzymes and the intermediates of the glycerol pathway. The results of this work will contribute significantly to our knowledge of the structure, function, regulation, and developmental biochemistry of this enzyme. Glycerol kinase occupies a position proximate to the interface of fat and carbohydrate metabolism. Therefore, the proposed experiments will not only provide information necessary for an understanding of this apparently rare inborn error of metabolism, with the intent of designing rational therapeutic strategies, but also will yield insight into the role of glycerol kinase in the development and regulation of fat and carbohydrate metabolism in man.